Discovery of , the First Direct Fast Skeletal Muscle Troponin Activator

Overview

Journal ACS Med Chem Lett

Publisher American Chemical Society

Specialty Chemistry

Date 2018 Apr 20

PMID 29670700

Citations 8

Authors

Scott E Collibee

Gustave Bergnes

Alexander Muci

William F Browne 4th

Marc Garard

Aaron C Hinken

Alan J Russell

Ion Suehiro

James Hartman

Raja Kawas

Pu-Ping Lu

Kenneth H Lee

David Marquez

Matthew Tomlinson

Donghong Xu

Adam Kennedy

Darren Hwee

Julia Schaletzky

Kwan Leung

Fady I Malik

David J Morgans Jr

Bradley P Morgan

Affiliations

Soon will be listed here.

Abstract

The identification and optimization of the first activators of fast skeletal muscle are reported. Compound was identified from high-throughput screening (HTS) and subsequently found to improve muscle function via interaction with the troponin complex. Optimization of for potency, metabolic stability, and physical properties led to the discovery of tirasemtiv (), which has been extensively characterized in clinical trials for the treatment of amyotrophic lateral sclerosis.

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